Drugs/Vaccines Flashcards
What kind of vaccine is the polio vaccine?
There are two types of polio vaccine. Life virus and whole cell (inactivated) vaccine.
1) Live virus used to be the standard vaccine used. However, it had a small chance (1 in 750k) to revert back to the active form -> causing polio infection.
The attenuated poliovirus in the Sabin vaccine replicates very efficiently in the gut, the primary site of wild poliovirus infection and replication, but the vaccine strain is unable to replicate efficiently within nervous system tissue.
2) Inactivated Whole Cell - The Salk vaccine utilized poliovirus grown in monkey kidney cells and inactivated with formalin. May be less effective / short lasting than live attenuated
What kind of vaccine is pertussis?
Whole cell inactivated or Acellular (dTAP = diphtheria toxoid, tetanus toxoid, acellular pertusis)
What kind of vaccine is the tetanus vaccine?
Tetanus toxoid
Tetanus toxoid is formalin-inactivated tetanus toxin. Efficacy is approximately 100% after 3 or 4 doses and a booster dose every 10 years.
What kind of vaccine is useful against diphtheria?
Diphtheria toxoid as part of dTAP.
While it is effective at immunizing people against the symptoms of diphtheria (since people gain ability to neutralize toxin), people can still be colonized by diphtheria and carry the bacteria
What kind of vaccine is influenza?
Two key types:
Trivalent/Quadravalent influenza vaccine (active against 2 straing so FluA, and 2 strains of FluB)
Influenza vaccines include an inactivated subunit vaccine, trivalent influenza vaccine (TIV) administered via the intramuscular or intradermal route and a live attenuated influenza vaccine (LAIV) administered by the intranasal route.
LAIV may have more adverse symptoms associated with it (fever, rash, etc.)
What kind of vaccine is Human Papillomavirus Vaccine?
Currently available vaccines include a nonavalent (6, 11, 16, 18, 31, 33, 45, 52, and 58) and a quadrivalent (6, 11, 16, 18) vaccines; each demonstrates efficacy of nearly 100% versus acquisition of infection with vaccine types and are extremely well tolerated. These are not therapeutic vaccines – they do not influence the course of disease if administered to someone already infected with those HPV types.
What kind of vaccine is useful against Herpes zoster?
The recombinant herpes zoster vaccine utilizes VZV glycoprotein E antigen with ASO1B adjuvant (Shingrix) is given as a 2-dose series, 2 months apart. Vaccine efficacy is 97% in adults age 50 to 69 years and 91% in adults age 70 years and older
What kind of vaccine is the varicella vaccine?
Varicella vaccine is a live, attenuated varicella zoster virus. It is highly effective: 90% coverage led to 83%-93% decline in varicella in the U.S.
What kind of vaccine is the BCG vaccine? (for TB)
BCG is attenuated (weakened) live Mycobacterium bovis (bovine tuberculosis). It is effective for only for a limited period of time (benefit lasts no more than 10-20 years) and booster doses are ineffective.
What kind of vaccine is the MMR vaccine?
Measles vaccine is a live virus vaccine, demonstrates 95% efficacy and resulting in lifelong immunity. The vaccination schedule includes a second dose in an effort to increase response rates closer to 100%. Nonresponse may be caused by antibody or damaged vaccine.
What kind of vaccine is useful against N. meningitidis?
There are two types of meningococcal vaccines available in the United States: Meningococcal conjugate vaccines (MenACWY) and serogroup B meningococcal vaccines (MenB).
What kind of vaccine is useful against H. influenza type B?
HiB vaccine
Haemophilus influenzae type b accounted for approximately up to 65% of cases of bacterial meningitis in the prevaccine era with a case fatality of 2%-5% despite of effective antimicrobial therapy and hearing impairment or neurologic sequelae in 15%-30% of survivors. The Hib conjugate polysaccharide vaccine has largely eradicated H. influenzae as a cause of meningitis in children.
What is a conjugate vaccine?
Conjugate vaccines combine a weak antigen with a strong antigen as a carrier so that the immune system has a stronger response to the weak antigen. Conjugate vaccines consist of antigens (polysaccharides or oligosaccharides) that are chemically coupled to a protein carrier. Coupling of the saccharides to protein converts polysaccharides to T-dependent antigens, which elicit robust immune responses in infants and adults. These “glycoconjugate” vaccines elicit T-cell help for B-cells that produce IgG antibodies to the conjugated polysaccharide
What are examples of beta-lactams? How do they function? How do bacteria gain resistance ?
Example Beta Lactams:
Penicillins
Cephalosporins
Monobactams (aztreonam)
Carbapenems
Glycopeptides (vancomycin) -> not a beta lactam but similar mechanism -> inhibit cell wall synthesis
Mechanism:
Beta-lactams kill bacteria by interfering with the synthesis of the bacterial cell wall.
Resistance Mechanism:
- Beta-lactamases are enzymes that destroy beta-lactam antibiotics, rendering them inactive.
- MRSA is resistant to beta-lactam antibiotics due to an alteration in penicillin-binding proteins. (PBP2)
What are lincosamides and what are their mechanism of action?
LINCOSAMIDES = clindamycin
Clindamycin binds to the 50S subunit of bacterial ribosomes and suppresses protein synthesis
Clindamycin typically has good gram-positive and anaerobic activity
Resistance:
Resistance to clindamycin can occur due to methylation of the 50S ribosome, which prevents attachment at the binding site.
How does trimethoprim-sulfamethoxazole (TMP-SMX) function?
Trimethoprim and sulfamethoxazole act on different steps of folate metabolism in bacterial cells (see Katzung, fig 46-2). Folate is on the pathway to purine and nucleic acid metabolism, so both agents ultimately interfere with the production of bacterial DNA.
How does linezolid work?
Time dependent (T > MIC)
Mechanism
Linezolid inhibits protein synthesis by preventing formation of the ribosome complex that initiates protein synthesis. Its unique binding site, located on 23S ribosomal RNA of the 50S subunit, results in no cross-resistance with other drug classes
Linezolid is active against gram-positive organisms including staphylococci (including MRSA)
Side effects:
Bone marrow suppression of all cell lines has been observed with use of linezolid; thrombocytopenia is more likely than leukopenia or anemia.
Mechanisms of Resistance
Resistance in enterococci and staphylococci is due to point mutations of the 23S rRNA.
How do Lipopeptides work?
Drug: Daptomycin
Mechanism of Action:
Daptomycin binds to the cell membrane and causes cell depolarization, loss of membrane potential due to potassium efflux, and cell death. Resistance to staphylococci and enterococci has been seen, but is not yet fully characterized.
Spectrum of Activity
Daptomycin is fairly similar to vancomycin in spectrum. It is active against most gram-positives, but has no activity against gram-negatives.
What is the mechanism of fluoroquinalone?
Names: “floxacin”
Concentration dependent
Levofloxacin, Ciprofloxacin, moxifloxacin
Mechanism:
Fluoroquinolones interfere with bacterial DNA synthesis by blocking two bacterial enzymes, topoisomerase II and IV. Fluoroquinolones bind to the enzyme–DNA complex, causing a conformational change in the enzyme. This leads to DNA cleavage by the enzyme while the continued presence of the fluoroquinolone prevents ligation of broken DNA strands.
Mechanism of Resistance:
Resistance to fluoroquinolones occurs due to point mutations in the target enzymes, which prevents the binding between the fluoroquinolone and the enzyme.
Bacteria can develop resistance by reducing the penetration of fluoroquinolones into the bacterial cell by removing porin channels
What is the mechanism of action for aminoglycosides?
Concentration Dependent (Cmax/MIC)
Aminoglycosides:
Mechanism of action:
Aminoglycosides irreversibly inhibit bacterial protein synthesis by binding to the 30S-subunit of the ribosome. 1) blocking the initiation complex; (2) causing misreading of mRNA so errors occur in the peptide chain; and (3) blocking movement of the ribosome so mRNA forms a complex with a single, nonfunctional monosome, rather than a polysome
Mechanism of Resistance:
There are several potential mechanisms of bacterial resistance to aminoglycosides. The most common involves enzyme deactivation of the aminoglycoside. An enzyme, called transferase, is produced that inactivates the aminoglycoside by adenylylation, acetylation, or phosphorylation.
What is the mechanism of action for macrolides?
Mechanism of Action:
Bind to 50S ribosomal subunit
Side Effects:
GI upset; Diarrhea; QTc prolongation
How do tetracyclines work?
Inhibit tRNA synthesis -> both time and concentration dependent (AUC/MIC)
Names:
doxycycline (iv and po); minocycline (po)
Mechanism of action:
Bind to 30S ribosomal subunit. Blocks binding of aminoacyl tRNA
Side Effects:
GI upset; diarrhea; photosensitivity; vestibular symptoms; increased skin pigmentation; tooth discoloration in children
Which of the following bind to the 30S subunit in bacteria?
AMINOGLYCOSIDES (azithromycin)
OXAZOLIDINONES (linezolid)
LINCOSAMIDES (clindamycin)
MACROLIDES
TETRACYCLINE (doxycycline)
BETA LACTAMS
AMINOGLYCOSIDES (azithromycin)
TETRACYCLINE (doxycycline)
Which of the following bind to the 23S/50S subunit in bacteria?
AMINOGLYCOSIDES (azithromycin)
OXAZOLIDINONES (linezolid)
LINCOSAMIDES (clindamycin)
MACROLIDES
TETRACYCLINE (doxycycline)
BETA LACTAMS
LIPOPEPTIDES
MACROLIDES (azithromycin)
OXAZOLIDINONES (linezolid)
LINCOSAMIDES (clindamycin)
Describe Concentration-dependent killing antibiotics_?_
What are example drugs which are concentration dependent?
Refers to antibiotic agents that kill most effectively when their Cmax is high.
Examples:
Aminoglycosides
Fluoroquinolones
What is Time-dependent killing?
Metric?
Examples?
Refers to antibiotic agents that kill best when their concentration persists above the MIC for longer durations of the dosing interval.
Metric?
T > MIC
Examples:
Beta lactams
Linezolid
What are cumulative dose drugs?
What are the examples?
Dosing schedule has no impact on efficacy for a third group of drugs, rather, cumulative dose matters. This is expressed by the total concentration to MIC ratio (AUC/MIC)
Examples:
Vancomycin
Daptomycin
Tetracyclines
Macrolides
What does bactericidal mean?
Bacteriostatic?
- Bacteriostatic agents: inhibit the growth of bacteria. Killing of the organism depends on host defense mechanisms
- Bacteriocidal agents: cause the death of bacteria. Killing of the organism depends less on host factors
- In general, cell-wall active agents are bactericidal and drugs that inhibit protein synthesis are bacteriostatic
- For immunocompromised or seriously ill patients, a bactericidal agent is preferred, if possible.
When should therapeutic drug monitoring be used?
Measuring serum concentration of antibiotics, or therapeutic drug monitoring (TDM), is not necessary in most circumstances, as there is a well-established relationship between dose and outcome. There are several situations in which TDM might be appropriate:
- A direct relationship exists between drug concentration and efficacy or toxicity
- Substantial interpatient variability exists in serum concentrations on standard doses
- There is a small difference between therapeutic and toxic serum concentrations (small therapeutic window)
- The clinical efficacy or toxicity of the drug is delayed or difficult to measure
- An accurate assay is available
